A Study of Subcutaneous Blinatumomab Administration in Acute Lymphoblastic Leukemia (ALL) Patients
B Cell Precursor Acute Lymphoblastic Leukemia
About this trial
This is an interventional treatment trial for B Cell Precursor Acute Lymphoblastic Leukemia focused on measuring R/R B-ALL, Blincyto®, AMG 103, Blinatumomab, Acute lymphoblastic leukemia (ALL)
Eligibility Criteria
Inclusion Criteria:
- Aged 18 years or older.
Participants with B-precursor ALL with any of the following:
- Either refractory to primary induction therapy or refractory to at least 1 salvage therapy OR
In untreated first, second, third or greater relapse or refractory relapse
- First Relapse is defined as achievement of first Complete Remission (CR) [CR1] during upfront therapy then relapse during or after continuation therapy
- Primary Refractory disease is defined as the absence of CR after standard induction therapy
- Refractory relapse is defined as lack of CR after salvage treatment
- Second relapse or later relapse is defined as relapse after achieving a second CR (CR2) in first or later salvage
- Refractory to salvage is defined as no attainment of CR after salvage
- Relapsed or Refractory at any time after first salvage therapy.
- Relapse at any time after allogenic hematopoietic stem cell transplant (HSCT).
- Greater than or equal to 5% blasts in the Bone Marrow.
- Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2.
- Participants with relapse or refractory B Cell ALL Ph+ disease and that are intolerant or refractory to prior tyrosine kinase inhibitors (TKIs) are eligible.
The above is a summary, other inclusion criteria details may apply.
Exclusion Criteria:
- Active ALL in the central nervous system (CNS). Presence of greater than 5 white blood cells per cubic millimeter in cerebrospinal fluid (CSF) with lymphoblasts present and/or clinical signs of CNS leukemia.
- History or presence of clinically relevant CNS pathology such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome or psychosis.
- Symptoms and/or signs that indicate an acute or uncontrolled chronic infection, any other disease or condition that could be exacerbated by the treatment or would complicate protocol compliance.
- History of malignancy (with certain exceptions) other than ALL within 3 years prior to start of protocol-specified therapy.
- Allogeneic HSCT within 12 weeks before the start of protocol-specified therapy.
- Cancer chemotherapy within 2 weeks before the start of protocol-specified therapy (with certain exceptions).
- Immunotherapy within 4 weeks before start of protocol-specified therapy. Prior failed CD19 directed therapy such as prior blinatumomab or CD19 CAR T cells will be allowed, if treatment ended more than 4 weeks prior to start of protocol therapy.
- Currently receiving treatment in, or less than 30 days since ending treatment on another investigational study(ies).
- Abnormal screening laboratory parameters.
- Female participant: Expected to breastfeed during treatment and for 96 hours after the last dose of treatment.
The above is a summary, other exclusion criteria details may apply.
Sites / Locations
- City of Hope National Medical CenterRecruiting
- New York University Langone HealthRecruiting
- University of Texas MD Anderson Cancer CenterRecruiting
- Fred Hutchinson Cancer Center
- University of WashingtonRecruiting
- Royal Adelaide HospitalRecruiting
- Monash Medical CentreRecruiting
- Austin Health, Austin HospitalRecruiting
- The Alfred HospitalRecruiting
- Universitaetsklinikum Allgemeines Krankenhaus WienRecruiting
- University of AlbertaRecruiting
- Vancouver General Hospital, Gordon and Leslie Diamond Health Care CentreRecruiting
- Centre Hospitalier Regional Universitaire de Lille - Hopital Claude HuriezRecruiting
- Centre Hospitalier Universitaire de NiceRecruiting
- Hopital Saint AntoineRecruiting
- Institut Universitaire du Cancer Toulouse OncopoleRecruiting
- Charite - Universitaetsmedizin Berlin, Campus Benjamin FranklinRecruiting
- Universitaetsklinikum KoelnRecruiting
- Universitaetsklinikum LeipzigRecruiting
- Universitaetsklinikum Tuebingen
- Universitatsklinikum UlmRecruiting
- Azienda Socio Sanitaria Territoriale Papa Giovanni XXIIIRecruiting
- Azienda Ospedaliera Universitaria di Bologna Policlinico S Orsola MalpighiRecruiting
- Azienda Socio Sanitaria Territoriale degli Spedali Civili di BresciaRecruiting
- IRCCS Ospedale San RaffaeleRecruiting
- Azienda Ospedaliera Policlinico Umberto IRecruiting
- National Cancer Center Hospital EastRecruiting
- Yokohama City University Medical CenterRecruiting
- Erasmus Medisch CentrumRecruiting
- Hospital Universitario Virgen del RocioRecruiting
- Complejo Asistencial Universitario de Salamanca. Hospital Universitario de SalamancaRecruiting
- Institut Catala d Oncologia Badalona Hospital Universitari Germans Trias i PujolRecruiting
- Hospital Clinico Universitario de ValenciaRecruiting
- Clinica Universidad de NavarraRecruiting
- Hospital Universitario 12 de OctubreRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Dose Escalation Phase: Blinatumomab Subcutaneous Formulation 1 (SC1)
Dose Expansion Phase: Blinatumomab SC1
Ph-IIC: Clinical PK Evaluation of SC Blinatumomab Formulations
Cohorts of at least 3 participants each will be treated with escalating doses of bilinatumomab to determine the maximum tolerated dose (MTD). The MTD will be defined as the dose for which the estimate of the toxicity rate from an isotonic regression (Yan et al, 2017) is closest to the target toxicity rate. Safety, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy will be assessed.
Up to 4 cohorts of participants with R/R B-ALL will be enrolled to the preliminary recommended phase 2 dose (RP2D) and schedule determined from dose escalation phase. Each cohort will aim to further assess safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy.
1 cohort of participants will be enrolled into the Ph-IIC arm. The clinical PK evaluation cohort (Ph-IIC) will be conducted to compare the PK of SC1 and SC2 formulations at the RP2D determined from the dose expansion phase, in participants with R/R B-ALL.